Premium
Regulation of Caveolin‐1 Trafficking by the Na/K‐ATPase/Src Interaction
Author(s) -
Cai Ting,
Xie Jeffrey,
Ye Qiqi,
Harris Tanoya L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.877.1
Subject(s) - endocytosis , microbiology and biotechnology , gene knockdown , proto oncogene tyrosine protein kinase src , phosphorylation , chemistry , transfection , tyrosine phosphorylation , v atpase , atpase , biology , cell , biochemistry , apoptosis , gene , enzyme
We have shown that graded knockdown of the Na/K‐ATPase increases endocytosis and mobility of caveolin‐1(Cav1), resulting in decreases in the plasma membrane pool of Cav1 (Cai, et al, J Cell Biol. 2008, 182:1153‐69). Moreover, the Na/K‐ATPase interacts and inhibits Src and knockdown of the Na/K‐ATPase increases cellular Src activity. Interestingly, inhibition of Src by PP2 reduced the endocytosis of Cav1 and partially restored the plasma membrane pool of Cav1, suggesting that Src‐mediated phosphorylation of Cav1 may play an important role in regulation of Cav1 trafficking. To further test this hypothesis, we mutated two well‐characterized phosphorylation sites in Cav1, namely Y14 and S80. Cells were transiently transfected with YFP‐tagged wild type Cav1 or Cav1 mutants. Confocal imaging analyses indicate that most Cav1S80A‐YFP, like Cav1wt‐YFP, resided in the cytosol in the Na/K‐ATPase knockdown cells. In contrast, most of the Cav1Y14F‐YFP mutant was detected in the plasma membrane. Consistently, particle tracking analyses demonstrated that Y14F mutation significantly reduced the mobility of YFP‐Cav1 vesicles. These findings suggest that the Na/K‐ATPase may regulate tyrosine phosphorylation of Cav1 Y14 and thus Cav1 trafficking by interacting and modulating cellular Src activity.